crossing96/oncoscreening huggingface dataset:
FGFR3 mutation analysis in voided urine samples to decrease cystoscopies and cost in nonmuscle invasive bladder cancer surveillance: a comparison of 3 strategies.	PURPOSE: We determined whether FGFR3 mutation analysis of voided urine samples would be cost-effective to partly replace cystoscopy in the surveillance of patients treated for nonmuscle invasive urothelial carcinoma. MATERIALS AND METHODS: In this decision analytical study we analyzed data on 70 Dutch patients with FGFR3 positive primary tumors and a median followup of 8.8 years. Surveillance strategies were compared in a Markov model. Modified surveillance consisted of FGFR3 mutation analysis of voided urine samples every 3 months, and cystoscopy at 3, 12 and 24 months. Standard surveillance was defined as cystoscopy every 3 months and minimal surveillance was defined as cystoscopy at 3, 12 and 24 months. Analysis was stratified for 3 risk profiles, including surveillance after 1) the primary tumor, 2) the first to third recurrence and 3) the fourth recurrence or more. Sensitivity analysis was performed to evaluate the impact of variations in cost, sensitivity and specificity. RESULTS: The probability of no recurrence after 2 years of surveillance after a primary tumor was higher for modified surveillance than for standard and minimal surveillance, eg after primary tumors (95.7% vs 95.0% and 93.9%, respectively). The total cost of surveillance after the primary tumor was lower for minimal and modified surveillance (€2,254 and €2,558, respectively) than for standard surveillance (€5,861). Results were robust to changing inputs over plausible ranges and consistent for each of the 3 risk profiles. CONCLUSIONS: Surveillance in which cystoscopy is partly replaced by FGFR3 mutation analysis of urine seems a safe, effective and cost-effective surveillance strategy. Further validation in larger cohorts is required.	bladder
Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4, and -9 in a case-control study with bladder cancer susceptibility in a North Indian population.	BACKGROUND AND AIMS: Impairment of the immune system may contribute to the risk for having cancer as Toll-like receptors are important for innate immunity. We examined the association between candidate disease-susceptibility polymorphisms in the single nucleotide polymorphism (SNPs) like TLR2 (-196 to-174del), TLR3 (C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes in patients with bladder cancer in a North Indian population. METHODS: SNPs were comprised of TLR2 (-196 to -174 Del), TLR3(C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes. Allelic and genotypic frequencies of these TLRs SNP from histopathologically confirmed patients of bladder cancer (n = 200) and unrelated healthy controls of similar ethnicity (n = 200) were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: In TLR2 I/D gene polymorphism, the combination of ID+DD showed a significant 3-fold increased risk (p = 0.001). TLR2 with heterozygous genotype ID showed a 3-fold risk and combination of heterozygous and variant genotype (ID+DD) also showed a 5-fold risk with tumor stage/grade of patients with bladder cancer. The other genotypes of TLR3, 4 and 9 did not exhibit any significant association with bladder cancer risk. CONCLUSIONS: Our results suggested the involvement of TLR2 (-196 to-174 del) in bladder cancer susceptibility; however, TLR3, 4 and 9 genes were not associated with risk of bladder cancer, implicating that polymorphisms in these tested TLRs genes are not likely to be associated with increased risk for developing bladder cancer. Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for the etiology of bladder cancer.	bladder
The association of RAS association domain family Protein1A (RASSF1A) methylation states and bladder cancer risk: a systematic review and meta-analysis.	RAS association domain family protein 1a (RASSF1A) is a putative tumor suppressor gene located on 3p21, has been regarded playing important roles in the regulation of different types of human tumors. Previous reports demonstrated that the frequency of RASSF1A methylation was significantly higher in patients group compared with controls, but the relationship between RASSF1A promoter methylation and pathological features or the tumor grade of bladder cancer remains controversial. Therefore, A meta-analysis of published studies investigating the effects of RASSF1A methylation status in bladder cancer occurrence and association with both pTNM (p, pathologic stage; T, tumor size; N, node status; M, metastatic status) and tumor grade in bladder cancer was performed in the study. A total of 10 eligible studies involving 543 cases and 217 controls were included in the pooled analyses. Under the fixed-effects model, the OR of RASSF1A methylation in bladder cancer patients, compared to non-cancer controls, was 8. 40 with 95%CI=4. 96-14. 23. The pooled OR with the random-effects model of pTNM and tumor grade in RASSF1A methylated patients, compared to unmethylated patients, was 0. 75 (95%CI=0. 28-1. 99) and 0. 39 (95%CI=0. 14-1. 09). This study showed that RASSF1A methylation appears to be an independent prognostic factor for bladder cancer. The present findings also require confirmation through adequately designed prospective studies.	bladder
Current perspectives in bladder cancer management.	More than 350,000 new cases of bladder cancer are diagnosed worldwide each year; the vast majority (> 90%) of these are transitional cell carcinomas (TCC). The most important risk factors for the development of bladder cancer are smoking and occupational exposure to toxic chemicals. Painless visible haematuria is the most common presenting symptom of bladder cancer; significant haematuria requires referral to a specialist urology service. Cystoscopy and urine cytology are currently the recommended tools for diagnosis of bladder cancer. Excluding muscle invasion is an important diagnostic step, as outcomes for patients with muscle invasive TCC are less favourable. For non-muscle invasive bladder cancer, transurethral resection followed by intravesical chemotherapy (typically Mitomycin C or epirubicin) or immunotherapy [bacillus Calmette-Guérin (BCG)] is the current standard of care. For patients failing BCG therapy, cystectomy is recommended; for patients unsuitable for surgery, the choice of treatment options is currently limited. However, novel interventions, such as chemohyperthermia and electromotive drug administration, enhance the effects of conventional chemotherapeutic agents and are being evaluated in Phase III trials. Radical cystectomy (with pelvic lymphadenectomy and urinary diversion) or radical radiotherapy are the current established treatments for muscle invasive TCC. Neoadjuvant chemotherapy is recommended before definitive treatment of muscle invasive TCC; cisplatin-containing combination chemotherapy is the recommended regimen. Palliative chemotherapy is the first-choice treatment in metastatic TCC.	bladder
Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03).	BACKGROUND: The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC. PATIENTS AND METHODS: One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events). RESULTS: The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%). CONCLUSIONS: Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number ACTRN12610000845033, www.anzctr.org.au.	bladder
Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for muscle-invasive bladder cancer.	AIM: Radical cystectomy plus platinum-based perioperative chemotherapy is a standard treatment for patients with clinically localized muscle-invasive bladder cancer. The standard perioperative chemotherapy is methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). However, no prospective randomized trial has been published that compares neoadjuvant and adjuvant chemotherapy for bladder cancer. Moreover, the efficacy of perioperative chemotherapy with gemcitabine plus cisplatin (GC) has not been clarified. In this study we have compared the clinical outcomes between neoadjuvant and adjuvant chemotherapy in patients receiving GC. METHODS: We retrospectively reviewed the records of patients who were scheduled to be treated with a radical cystectomy plus perioperative chemotherapy with GC from 2005 to 2010 at our institution. The primary outcome measure was recurrence-free survival (RFS). RESULTS: A total of 42 patients received perioperative chemotherapy with GC (25 neoadjuvant, 17 adjuvant). The median number of cycles of GC administered to the two groups was not significantly different. The median duration of follow up was 28.6 months. During the follow-up period, recurrence was observed in nine and three patients in the neoadjuvant and adjuvant groups, respectively. The RFS rate at median follow up was 67 and 76% in the neoadjuvant and adjuvant groups, respectively. No significant difference in RFS at median follow up was observed between the two groups (P = 0.124). CONCLUSION: Our results showed no statistically significant difference in RFS between neoadjuvant and adjuvant GC chemotherapy for muscle-invasive bladder cancer. We expect to validate these findings in a prospective randomized trial.	bladder
FTIR microspectroscopy of selected rare diverse sub-variants of carcinoma of the urinary bladder.	Urothelial carcinomas of the bladder are a heterogeneous group of tumours, although some histological sub-variants are rare and sparsely reported in the literature. Diagnosis of sub-variants from conventional urothelial carcinoma can be challenging, as they may mimic the morphology of other malignancies or benign tumours and therefore their distinction is important. For the first time, the spectral pathology of some of these sub-variants has been documented by infrared microspectroscopy and an attempt made to profile their biochemistry. It is important not only to identify and separate the cancer-associated epithelial tissue spectra from common tissue features such as stroma or blood, but also to detect the signatures of tumour sub-variants. As shown, their spectroscopic signals can change dramatically as a consequence of differentiation. Example cases are discussed and compared with histological evaluations.	bladder
Pooled analysis of clinical outcomes with neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer.	PURPOSE: Neoadjuvant chemotherapy for muscle invasive bladder cancer has been shown to confer a survival advantage in phase III studies. Although cisplatin and gemcitabine are often used in this setting, a comprehensive evaluation of this regimen is lacking. In this review we summarize the efficacy of neoadjuvant cisplatin and gemcitabine chemotherapy for muscle invasive bladder cancer based on currently published studies. MATERIALS AND METHODS: A systematic literature review was conducted in April 2012 searching MEDLINE® databases. Articles were selected if they included patients with muscle invasive bladder cancer, evaluated the combination of cisplatin and gemcitabine as neoadjuvant treatment, and reported pathological data after cystectomy. Cisplatin and gemcitabine dosing regimens and clinical data were further summarized using weighted averages. RESULTS: Seven studies encompassing 164 patients were published between 2007 and 2012. The majority of patients (79%) received cisplatin and gemcitabine on a 21-day cycle. A weighted average of 19.2 lymph nodes was obtained at cystectomy, and 29.7% of patients were found to have pN1 disease. Pathological down staging to pT0 and less than pT2 occurred in 42 (25.6%) and 67 (46.5%) patients, respectively. CONCLUSIONS: Neoadjuvant cisplatin and gemcitabine yield appreciable pathological response rates in patients with muscle invasive bladder cancer. Since pathological response has been implicated as a potential surrogate for survival in muscle invasive bladder cancer, these data suggest that neoadjuvant cisplatin and gemcitabine may warrant further prospective assessment.	bladder
[The intravesical recurrence after 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) following transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer].	PURPOSE: We estimated the results of 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) following transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer retrospectively. PATIENTS AND METHODS: Through March 1995 to April 2009, a total of 184 patients were instilled 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) (30 mg/40 ml in disinfected distilled water) started within a few hours after TURBT. 184 patients were diagnosed as untreated fresh non-muscle-invasive urothelial bladder cancer with no concomitant carcinoma in situ (CIS), no concurrent upper urinary tract urothelial cancer and no past history of upper urinary tract urothelial cancer. Number of tumors, tumor size, tumor grade and clinical tumor stage were analyzed in relation to tumor recurrence by univariate and multivariate analyses. Median follow-up were 55.1 months. RESULTS: Using EAU guideline on non-muscle invasive urothelial carcinoma of the bladder, 168 patients were classified at intermediate risk of tumor recurrence, 14 patients were at low risk of tumor recurrence and 2 patients were at high risk of tumor recurrence. The shape of non-recurrence rate curve showed two phase decrease pattern, namely, early hasty decrease within 1.5 or two years and late gentle decrease thereafter. The 1, 2, 3, 5-year non-recurrence rate were 82.7%, 75.3%, 72.3% and 67.4% respectively. The 3-year non-recurrence rate of low score group (recurrence score 1-3) at intermediate risk of tumor recurrence was 85.3%. Univariate analysis revealed that number of tumors, tumor grade and clinical tumor stage were related to tumor recurrence (p<0.05). By multivariate analysis, number of tumors and clinical tumor stage were related to tumor recurrence (p<0.05). CONCLUSIONS: In patients of low score group at intermediate risk of tumor recurrence without grade 3 urothelial carcinoma and concomitant bladder CIS, 3-day consecutive intravesical instillation of pirarubicine hyorochloride (THP) following TURBT for non-muscle-invasive bladder cancer would be a significant adjuvant therapy. But in patients of high score group at intermediate risk of tumor recurrence, it seemed better to do additional maintenance intravesical chemotherapy or intravesical BCG therapy.	bladder
Carcinoma in situ of urinary bladder: incidence, treatment and clinical outcomes during ten-year follow-up.	Bladder carcinoma in situ (CIS) is a rare, high-grade intraepithelial neoplasm with a high tendency of progression and unpredictable clinical course. The aim of this study was to evaluate the incidence, treatment and clinical outcome of patients with CIS during a 10-year period. Medical records of 1062 patients with primary bladder cancer and 847 patients with recurrent bladder cancer that underwent tumor resection at Department of Urology, Split University Hospital Center, Split, Croatia, between January 2001 and December 2010, were analyzed. Among all treated patients with primary bladder neoplasms, 51 (4.8%) had CIS. Primary CIS was diagnosed in 18 (1.7%) and concomitant CIS in 33 (3.1%) patients. In the same period, 847 patients with recurrent tumors were treated by transurethral resection (TUR), 12 (1.4%) of them with secondary CIS. Clinical course was followed-up in 15 patients with primary CIS and 21 patients with concomitant (TaT1) CIS. BCG immunotherapy was applied in 12 patients with primary and 17 patients with concomitant CIS. After median follow-up of 50 months, 9 patients with primary CIS had no sign of disease, 4 progressed, 1 had recurrence and 1 died. After median follow-up of 37 months, 13 (62%) patients with concomitant CIS had complete response, 3 progressed (14%), 1 had recurrence (4%) and 4 patients died, however, only 2 (10%) of these due to bladder cancer. Of all patients receiving BCG immunotherapy, 8 (27%) had significant side effects. The incidence and treatment of patients with CIS of urinary bladder in our institution is comparable to other recent literature reports.	bladder
Nuclear E-cadherin expression is associated with the loss of membranous E-cadherin, plasmacytoid differentiation and reduced overall survival in urothelial carcinoma of the bladder.	BACKGROUND: Loss of E-cadherin represents a hallmark of plasmacytoid differentiation. We analyzed the effect of membranous E-cadherin loss and its nuclear accumulation in patients with locally advanced conventional urothelial carcinoma (UC) who were treated with radical cystectomy and adjuvant chemotherapy. METHODS: A total of 247 formalin-fixed, paraffin-embedded tumor samples were reviewed to detect histological variants of UC. Immunohistochemical staining of E-cadherin was performed and analyzed for membranous and nuclear expression. The correlation between E-cadherin expression and histology was assessed, and overall survival (OS) was analyzed with univariate and multivariate Cox regression and Kaplan-Meier analyses. Correlation of nuclear E-cadherin to tumor stage (pT), lymph node metastasis (pN), histologic subtype, and chemotherapy was performed by Fisher's exact test. RESULTS: Membranous and nuclear E-cadherin expression was strongly correlated to plasmacytoid urothelial carcinoma (PUC) (p < 0.001). Complete loss of membranous E-cadherin expression was observed in 76.2 % of PUCs, 11.1 % of conventional UCs, and 0 % of micropapillary urothelial carcinoma (MPCs). Nuclear accumulation was found in 47.6 % of PUCs, 10 % of MPCs, and 1.8 % of UCs. Sixty-two percent of all tumors with negative membranous E-cadherin expression and nuclear accumulation were PUCs (p = 0.035). In a Kaplan-Meier analysis, mean survival with nuclear E-cadherin expression was 31.9 months [95 % confidence interval (CI) 16.1-47.6] of patients without nuclear staining 61 months (95 % CI 53.5-67.7; p = 0.045). A univariate Cox regression analysis showed that nuclear E-cadherin accumulation was associated with a 2-fold increase in risk of death (95 % CI 1.03-4.06; p = 0.04). In multivariate Cox regression analysis adjusted to type of chemotherapy, tumor stage, and tumor grade, the hazard ratio for patients with nuclear E-cadherin was 2.03 (95 % CI 1.00-4.121; p = 0.050). CONCLUSIONS: Nuclear E-cadherin is associated with PUCs and is suggested to be an independent prognostic factor in advanced UC.	bladder
Clipping the extremity of ureter prior to nephroureterectomy is effective in preventing subsequent bladder recurrence after upper urinary tract urothelial carcinoma.	BACKGROUND: Bladder recurrent disease is still a challenge in the treatment of upper tract urothelial carcinoma (UTUC). This controlled study aims to investigate the efficacy of early clipping of the distal ureter prior to nephroureterectomy (NU) to prevent bladder recurrence after UTUC. METHODS: Patients with clinical diagnosis of UTUC were subjected to open trans-peritoneal NU and were randomly divided into two groups. One group received modified NU: clipping the distal ureter prior to NU; while the other group underwent traditional standard NU. Subsequent bladder recurrence was the primary endpoint. RESULTS: From January 2007 to December 2009, 85 eligible cases were enrolled in this study. Modified NU and standard NU were performed on 42 and 43 patients, respectively. Operation time ((215.73 ± 21.26) minutes vs. (220.19 ± 15.35) minutes), blood loss ((105.15 ± 11.32) ml vs. (110.12 ± 9.07) ml), transfusion event (11.20% vs. 9.78%), and the in-patient time (10.0 days vs 9.5 days) were not significant between the two groups. After a median follow-up of 28 months (5 - 60), six (14.3%) cases who received modified NU had bladder recurrence, which was significantly lower compared with 15 (34.9%) patients from the group that underwent standard NU (P = 0.026). In univariate and multivariate analysis, tumor grade (HR 4.33, 95%CI 2.66 - 6.30, P = 0.01) and operation type (HR 2.35, 95%CI 1.53 - 3.48, P = 0.041) were independent risk factors for subsequent bladder recurrence after UTUC. CONCLUSIONS: Clipping the distal ureter at the beginning of NU significantly reduces bladder recurrence after UTUC. It is reasonable to conclude that clipping the distal portion of ureter trans-peritoneal is an effective surgical procedure for the treatment of UTUC.	bladder
Selective immunohistochemical markers to distinguish between metastatic high-grade urothelial carcinoma and primary poorly differentiated invasive squamous cell carcinoma of the lung.	CONTEXT: Distinction between primary lung carcinomas and metastases from other sites, especially the urinary tract, is a common diagnostic dilemma. As urothelial carcinomas can demonstrate a broad range of morphology and frequently demonstrate squamous differentiation, discerning metastatic urothelial carcinoma to the lung from primary pulmonary squamous cell carcinoma can be challenging. OBJECTIVE: To investigate immunostains that may aid in the distinction of urothelial carcinoma metastatic to the lung. DESIGN: Staining patterns of 14 markers in primary urothelial carcinoma of the bladder and primary squamous cell carcinoma of the lung were examined to establish a diagnostic panel. These antibodies were subsequently tested on tumors taken from 30 patients with a paired urinary tract and metastatic lung lesion. RESULTS: The best markers to distinguish poorly differentiated metastatic urothelial carcinoma from primary pulmonary squamous cell carcinoma were CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III, with the utility of the latter dependent upon the quantity of tissue available for analysis. The observed percentage positive staining in nonmetastatic urothelial carcinoma versus primary pulmonary squamous cell carcinoma with these antibodies was as follows: CK7 (100% versus 33%), CK20 (54% versus 7%), GATA-3 (78% versus 23%), CK14 (32% versus 77%), desmoglein-3 (11% versus 87%), and uroplakin III (14% versus 0%). Similar expression patterns were observed among the paired cases. CONCLUSION: When interpreted in correlation with clinical history and histomorphology, a panel of immunostains including CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III may be a useful adjunct in the distinction of metastatic urothelial carcinoma to the lung.	bladder